Molecule Information

General Information of the Molecule (ID: Mol01935)

• Name: Diacylglycerol kinase iota (DGKI) ,Homo sapiens
• Synonyms: DGKI
• Molecule Type: Protein
• Gene Name: DGKI
• Gene ID: 9162
• Location: chr7:137,381,037-137,847,092[-]
• Sequence:
  MDAAGRGCHLLPLPAARGPARAPAAAAAAAASPPGPCSGAACAPSAAAGAGAMNPSSSAG
  EEKGATGGSSSSGSGAGSCCLGAEGGADPRGAGSAAAAGAAALDEPAAAGQKEKDEALEE
  KLRNLTFRKQVSYRKAISRAGLQHLAPAHPLSLPVANGPAKEPRATLDWSENAVNGEHLW
  LETNVSGDLCYLGEENCQVRFAKSALRRKCAVCKIVVHTACIEQLEKINFRCKPTFREGG
  SRSPRENFVRHHWVHRRRQEGKCKQCGKGFQQKFSFHSKEIVAISCSWCKQAFHNKVTCF
  MLHHIEEPCSLGAHAAVIVPPTWIIKVKKPQNSLKASNRKKKRTSFKRKASKRGMEQENK
  GRPFVIKPISSPLMKPLLVFVNPKSGGNQGTKVLQMFMWYLNPRQVFDLSQEGPKDALEL
  YRKVPNLRILACGGDGTVGWILSILDELQLSPQPPVGVLPLGTGNDLARTLNWGGGYTDE
  PVSKILCQVEDGTVVQLDRWNLHVERNPDLPPEELEDGVCKLPLNVFNNYFSLGFDAHVT
  LEFHESREANPEKFNSRFRNKMFYAGAAFSDFLQRSSRDLSKHVKVVCDGTDLTPKIQEL
  KFQCIVFLNIPRYCAGTMPWGNPGDHHDFEPQRHDDGYIEVIGFTMASLAALQVGGHGER
  LHQCREVMLLTYKSIPMQVDGEPCRLAPAMIRISLRNQANMVQKSKRRTSMPLLNDPQSV
  PDRLRIRVNKISLQDYEGFHYDKEKLREASISDWLRTIAGELVQSFGAIPLGILVVRGDC
  DLETCRMYIDRLQEDLQSVSSGSQRVHYQDHETSFPRALSAQRLSPRWCFLDDRSQEHLH
  FVMEISQDEIFILDPDMVVSQPAGTPPGMPDLVVEQASGISDWWNPALRKRMLSDSGLGM
  IAPYYEDSDLKDLSHSRVLQSPVSSEDHAILQAVIAGDLMKLIESYKNGGSLLIQGPDHC
  SLLHYAAKTGNGEIVKYILDHGPSELLDMADSETGETALHKAACQRNRAVCQLLVDAGAS
  LRKTDSKGKTPQERAQQAGDPDLAAYLESRQNYKVIGHEDLETAV
• Function: Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable). Has probably no preference for any of the diacylglycerols in terms of the acyl chain composition, especially for the acyl chain at the sn-2 position. By controlling the diacylglycerol/DAG-mediated activation of RASGRP3, negatively regulates the Rap1 signaling pathway. May play a role in presynaptic diacylglycerol/DAG signaling and control neurotransmitter release during metabotropic glutamate receptor-dependent long-term depression.
• Uniprot ID: DGKI_HUMAN
• Ensembl ID: ENSG00000157680
• HGNC ID: HGNC:2855

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cladribine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Acute lymphocytic leukemia [1]

• Resistant Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Resistant Drug: Cladribine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain; 1280
• Mechanism Description: Cladribine cannot be deaminated by adenosine deaminase(ADA) and is phosphorylated to cladribine-MP by dCK. Cladribine self potentiates its own activation by activation of dCK. The cytotoxicity mainly depends on the accumulation of cladribine-TP after phosphoryl-ation of cladribine-MP by nucleoside MP kinase and nucleoside diphosphate kinase in the cells. Down regulation of all activating enzymes such as dCK or dGK due to loss of expression or through mutation, has been shown to cause resistance to cladribine. However, the most frequently described form of acquired resistance to cladribine in vitro is dCK de ciency and reduction in dCK activity is probably the major determinant of cladribine resistance.

References

• Ref 1: Pharmacological basis for cladribine resistance .Leuk Lymphoma. 2003 Oct;44(10):1705-12. doi: 10.1080/1042819031000099698. 10.1080/1042819031000099698